1,017 research outputs found
Does a Joint Academic-Practitioner Review Reconcile Rigor and Relevance?
A substantial body of literature discusses the so-called rigor-relevance gap
in management science and possible ways of overcoming it. A frequently
advocated approach, in line with Gibbons, Limoges, Nowotny, Schwartz, and
Trowâs âMode 2â idea of creating âhybrid fora,â is the introduction of joint
academicâpractitioner review processes in management journals. In an empirical
case study of one of the oldest management journals in the world, the authors
show that the demands of academic and practitioner reviewers are hardly
compatible, and, to some extent, inversely correlated. In contrast to other
studies, here the authors show that the reason for the tension between
academics and practitioners with regard to this issue does not lie in
differences in the evaluation criteria of each group. Rather, the different
worldviews of academics and practitioners lead to different interpretations of
these criteria and a striking incongruence between the two groupsâ ideas of
practical relevance
Interleukin-18 Mediates Immune Responses to Campylobacter jejuni Infection in Gnotobiotic Mice
Background Human Campylobacter jejuni infections are progressively rising
worldwide. Information about the molecular mechanisms underlying
campylobacteriosis, however, are limited. In the present study we investigated
whether cytokines such as IL-23, IL-22 and IL-18, which share pivotal
functions in host immunity, were involved in mediating intestinal and systemic
immunopathological responses upon C. jejuni infection. Methodology/Principal
Findings To assure stable infection, gnotobiotic (i.e. secondary abiotic) IL-
23p19-/-, IL-22-/- and IL-18-/- mice were generated by broad-spectrum
antibiotic treatment. Following peroral C. jejuni strain 81â176 infection,
mice of all genotypes harbored comparably high pathogenic loads in their
intestines. As compared to wildtype controls, however, IL-18-/- mice displayed
less distinct C. jejuni induced sequelae as indicated by less pronounced large
intestinal shrinkage and lower numbers of apoptotic cells in the colonic
epithelial layer at day 8 postinfection (p.i.). Furthermore, lower colonic
numbers of adaptive immune cells including regulatory T cells and B
lymphocytes were accompanied by less distinct secretion of pro-inflammatory
cytokines such as TNF and IFN-Îł and lower IL-17A mRNA expression levels in
colonic ex vivo biopsies of infected IL-18-/- as compared to wildtype mice.
Upon C. jejuni infection, colonic IL-23p19 expression was up-regulated in
IL-18-/- mice only, whereas IL-22 mRNA levels were lower in uninfected and
infected IL-23p19-/- as well as infected IL-18-/- as compared to respective
wildtype control mice. Remarkably, not only intestinal, but also systemic
infection-induced immune responses were less pronounced in IL-18-/- mice as
indicated by lower TNF, IFN-Îł and IL-6 serum levels as compared to wildtype
mice. Conclusion/Significance We here show for the first time that IL-18 is
essentially involved in mediating C. jejuni infection in the gnotobiotic mouse
model. Future studies need to further unravel the underlying regulatory
mechanisms orchestrating pathogen-host interaction
The InMAS Approach
The Internet Malware Analysis System (InMAS) is a modular platform for distributed, large-scale monitoring of malware on the Internet. InMAS integrates diverse tools for malware collection (using honeypots)
and malware analysis (mainly using dynamic analysis). All collected information is aggregated and accessible through an intuitive and easy-to-use web interface. In this paper, we provide an overview of the structure of InMAS and the various tools it integrates. We also introduce the web frontend that displays all information on different levels of abstraction, from a coarse-grained overview down to highly detailed information on demand
Survey of small intestinal and systemic immune responses following murine Arcobacter butzleri infection
Background Arcobacter (A.) butzleri has been described as causative agent for
sporadic cases of human gastroenteritis with abdominal pain and acute or
prolonged watery diarrhea. In vitro studies revealed distinct adhesive,
invasive and cytotoxic properties of A. butzleri. Information about the
underlying immunopathological mechanisms of infection in vivo, however, are
scarce. The aim of this study was to investigate the immunopathological
properties of two different A. butzleri strains in a well-established murine
infection model. Results Gnotobiotic IL-10 â/â mice, in which the intestinal
microbiota was depleted by broad-spectrum antibiotic treatment, were perorally
infected with two different A. butzleri strains isolated from a diseased
patient (CCUG 30485) or fresh chicken meat (C1), respectively. Eventhough
bacteria of either strain could stably colonize the intestinal tract at day 6
and day 16 postinfection (p.i.), mice did not exert infection induced symptoms
such as diarrhea or wasting. In small intestines of infected mice, however,
increased numbers of apoptotic cells could be detected at day 16, but not day
6 following infection with either strain. A strain-dependent influx of
distinct immune cell populations such as T and B cells as well as of
regulatory T cells could be observed upon A. butzleri infection which was
accompanied by increased small intestinal concentrations of pro-inflammatory
cytokines such as TNF, IFN-Îł, MCP-1 and IL-6. Remarkably, inflammatory
responses following A. butzleri infection were not restricted to the
intestinal tract, given that the CCUG 30485 strain induced systemic immune
responses as indicated by increased IFN-Îł concentrations in spleens at day 6,
but not day 16 following infection. Conclusion Upon peroral infection A.
butzleri stably colonized the intestinal tract of gnotobiotic IL-10 â/â mice.
The dynamics of distinct local and systemic inflammatory responses could be
observed in a strain-dependent fashion pointing towards an immunopathogenic
potential of A. butzleri in vivo. These results indicate that gnotobiotic
IL-10 â/â mice are well suited to further investigate the molecular mechanisms
underlying arcobacteriosis in vivo
Arcobacter butzleri Induce Colonic, Extra-Intestinal and Systemic Inflammatory Responses in Gnotobiotic IL-10 Deficient Mice in a Strain-Dependent Manner
BACKGROUND: The immunopathological impact of human Arcobacter (A.) infections
is under current debate. Episodes of gastroenteritis with abdominal pain and
acute or prolonged watery diarrhea were reported for A. butzleri infected
patients. Whereas adhesive, invasive and cytotoxic capacities have been
described for A. butzleri in vitro, only limited information is available
about the immunopathogenic potential and mechanisms of infection in vivo.
METHODOLOGY/PRINCIPAL FINDINGS: Gnotobiotic IL-10-/- mice were generated by
broad-spectrum antibiotic treatment and perorally infected with the A.
butzleri strains CCUG 30485 and C1 shown to be invasive in cell culture
assays. Bacterial colonization capacities, clinical conditions, intestinal,
extra-intestinal and systemic immune responses were monitored at day six and
16 postinfection (p.i.). Despite stable intestinal A. butzleri colonization at
high loads, gnotobiotic IL-10-/- mice were virtually unaffected and did not
display any overt symptoms at either time point. Notably, A. butzleri
infection induced apoptosis of colonic epithelial cells which was paralleled
by increased abundance of proliferating cells. Furthermore A. butzleri
infection caused a significant increase of distinct immune cell populations
such as T and B cells, regulatory T cells, macrophages and monocytes in the
colon which was accompanied by elevated colonic TNF, IFN-Îł, nitric oxide (NO),
IL-6, IL-12p70 and MCP-1 concentrations. Strikingly, A. butzleri induced
extra-intestinal and systemic immune responses as indicated by higher NO
concentrations in kidney and increased TNF, IFN-Îł, IL-12p70 and IL-6 levels in
serum samples of infected as compared to naive mice. Overall, inflammatory
responses could be observed earlier in the course of infection by the CCUG
30485 as compared to the C1 strain. CONCLUSION/SIGNIFICANCE: Peroral A.
butzleri infection induced not only intestinal but also extra-intestinal and
systemic immune responses in gnotobiotic IL-10-/- mice in a strain-dependent
manner. These findings point towards an immunopathogenic potential of A.
butzleri in vertebrate hosts
The role of serine protease HtrA in acute ulcerative enterocolitis and extra-intestinal immune responses during Campylobacter jejuni infection of gnotobiotic IL-10 deficient mice
Campylobacter jejuni infections have a high prevalence worldwide and represent a significant socioeconomic burden. C. jejuni can cross the intestinal epithelial barrier as visualized in biopsies derived from human patients and animal models, however, the underlying molecular mechanisms and associated immunopathology are still not well understood. We have recently shown that the secreted serine protease HtrA (high temperature requirement A) plays a key role in C. jejuni cellular invasion and transmigration across polarized epithelial cells in vitro. In the present in vivo study we investigated the role of HtrA during C. jejuni infection of mice. We used the gnotobiotic IL-10â/â mouse model to study campylobacteriosis following peroral infection with the C. jejuni wild-type (WT) strain NCTC11168 and the isogenic, non-polar NCTC11168ÎhtrA deletion mutant. Six days post infection (p.i.) with either strain mice harbored comparable intestinal C. jejuni loads, whereas ulcerative enterocolitis was less pronounced in mice infected with the ÎhtrA mutant strain. Moreover, ÎhtrA mutant infected mice displayed lower apoptotic cell numbers in the large intestinal mucosa, less colonic accumulation of neutrophils, macrophages and monocytes, lower large intestinal nitric oxide, IFN-Îł, and IL-6 as well as lower TNF-α and IL-6 serum concentrations as compared to WT strain infected mice at day 6 p.i. Notably, immunopathological responses were not restricted to the intestinal tract given that liver and kidneys exhibited mild histopathological changes 6 days p.i. with either C. jejuni strain. We also found that hepatic and renal nitric oxide levels or renal TNF-α concentrations were lower in the ÎhtrA mutant as compared to WT strain infected mice. In conclusion, we show here that the C. jejuni HtrA protein plays a pivotal role in inducing host cell apoptosis and immunopathology during murine campylobacteriosis in the gut in vivo
- âŠ